Antipsychotic drugs increase the biosynthesis of dopamine (DA) in dopaminergic nerve terminals and also the firing rate of DA neurones in pars compacta of substantia nigra. Here we report that an increase in the affinity of striatal tyrosine hydroxylase (TH) for pteridine cofactors participates in the increase of DA synthesis occurring in rats injected with antipsychotics. The action of antipsychotics on this short-term change of TH requires the blockade of dopamine receptors, involves cholinergic mechanism and is abolished by transection of the nigra striatal connections. Intranigral application of muscimol (a GABA mimetic compound) also blocks the activation of TH induced by haloperidol. These results suggest that a multineuronal system involving GABAergic terminals impinging upon the dopaminergic cell body of substantia nigra is repressed during treatment with antipsychotics.